Hormonal Regulation of Feeding, Metabolism, Growth and Reproduction in Fish

我的发现研究计划的长期目标是通过表征调节鱼类新陈代谢、生长和繁殖的新型激素来创造新的知识。在过去的五年里，我们发现了许多激素的生物学作用。其中，Nesfatin-1和NLP是两种多功能多肽，可调节鱼类的摄食、代谢、生长和繁殖。此外，还鉴定了三种调节摄食和代谢的生长因子。虽然Nesfatin-1和NLP具有多种生物学作用，但它们是否对维持鱼类生理是必需的尚不清楚。NLP-1和NLP的作用机制尚不清楚。生长因子是否调节鱼类的繁殖和生长尚不清楚。这项建议建立在我们最初的发现基础上，是我们迄今为止研究的合乎逻辑和可行的延伸。它的目标是进行下一组研究，以填补关于鱼类中这些重要调控因子的几个知识空白。在目标1下，我们将利用遗传工具，删除斑马鱼中的nesifatin-1和NLP基因，并确定这两种多肽在维持代谢动态平衡、生长和繁殖方面的关键程度。预计一个或两个多肽的丢失会导致新陈代谢、生长和生殖的紊乱。在目标2中，还将使用能够梳理出特定受体和途径的药理学试剂和遗传工具来确定NLP-1和NLP的作用机制。我们认为，细胞表面受体和专属的细胞内信号对NLP-1和NLP的作用非常重要。目的3通过测定生长因子对配子发育、卵泡成熟、生长、体重和调节这些过程的主要激素的影响，探讨生长因子在生长和生殖调节中的作用。我们希望这些以前未知的生长因子能够刺激斑马鱼的生长和繁殖，以及支持这种生长和繁殖的激素环境。通过这项研究创造的新的基础知识将有助于重新定义和更新我们目前对鱼类生物学的理解。通过帮助了解这些激素如何调节包括家畜在内的其他物种的重要过程，这可能是有益的。该项目的成果预计将有助于制定新的战略，以促进水产养殖中鱼类的生长和繁殖，从而促进可持续性和粮食安全。这项研究为培训下一代年轻研究人员，特别是女性和科学界代表性不足的人提供了极好的机会。他们将为加拿大劳动力和经济所需的高素质人才库做出贡献。总体而言，拟议的研究计划将产生相当多的新知识，同时间接地为加拿大的经济和可持续发展努力做出重大贡献。

The long-term goal of my discovery research program is to create new knowledge through the characterization of novel hormones that regulate metabolism, growth and reproduction in fish. In the past five years, we discovered the biological actions of numerous hormones. Among them, nesfatin-1 and nesfatin-1-like peptide (Nlp) are two multifunctional peptides that were found to regulate feeding, metabolism, growth and reproduction in fish. In addition, three growth factors that regulate feeding and metabolism were characterized. While nesfatin-1 and Nlp have multiple biological actions, whether they are essential to maintain fish physiology is unknown. The mechanism of action of nesfatin-1 and Nlp is poorly understood. Whether growth factors regulate reproduction and growth in fish is unclear. This proposal builds on our original discoveries, and it is a logical and feasible extension of our research to date. It aims to conduct the next set of studies to fill several knowledge gaps on these important regulators in fish. Under objective 1, using genetic tools, we will delete nesfatin-1 and Nlp genes in zebrafish and determine how critical these two peptides are in maintaining metabolic homeostasis, growth and reproduction. It is anticipated that the loss of one or both peptides lead to disturbed metabolism, growth and reproduction. In objective 2, the mechanism of action of nesfatin-1 and Nlp will also be determined using pharmacological agents and genetic tools that can tease out specific receptors and pathways. We believe that a cell surface receptor and dedicated intracellular signals are important for nesfatin-1 and Nlp action. Objective 3 will explore the role of growth factors in regulating growth and reproduction will be studied by measuring the effects of these peptides on gamete development, ovarian follicle maturation, growth, body weight and major hormones that regulate these processes. We expect these previously uncharacterized growth factors to stimulate both growth and reproduction and the hormonal milieu that supports it in zebrafish. The novel fundamental knowledge created though this research will help redefine and update our current understanding of fish biology. It could be beneficial by helping learn how these hormones regulate important processes in other species including domestic animals. The outcomes of this program are expected to help develop new strategies to enhance fish growth and reproduction in aquaculture, thus contributing to sustainability and food security. This research provides remarkable opportunities for training the next generation of young researchers, especially women and those underrepresented in science. They will contribute to the pool of highly qualified personnel required by Canada's workforce and economy. Overall, the proposed research program will generate considerable new knowledge while contributing indirectly, yet significantly to the economy and sustainability efforts in Canada.